Add-on spironolactone as antagonist of the NRG1-ERBB4 signaling pathway for the treatment of schizophrenia : Study design and methodology of a multicenter randomized, placebo-controlled trial
© 2020 The Author(s)..
BACKGROUND: Preclinical studies recently showed that the mineralocorticoid antagonist spironolactone acts also as an antagonist of the NRG1-ERBB4 signaling pathway and improves schizophrenia-like behaviour in Nrg1 transgenic mouse model. As this signaling pathway is critically linked to the pathophysiology of schizophrenia, especially in the context of working-memory dysfunction, spironolactone may be a novel treatment option for patients with schizophrenia targeting cognitive impairments.
AIMS: To evaluate whether spironolactone added to an ongoing antipsychotic treatment improves cognitive functioning in schizophrenia.
METHODS: The add-on spironolactone for the treatment of schizophrenia trial (SPIRO-TREAT) is a multicenter randomized, placebo-controlled trial with three arms (spironolactone 100 mg, spironolactone 200 mg and placebo). Schizophrenia patients are treated for three weeks and then followed-up for additional nine weeks. As primary outcome, we investigate changes in working memory before and at the end of the intervention phase. We will randomize 90 patients. Eighty-one patients are intended to reach the primary endpoint measure at the end of the three-week intervention period. Secondary endpoints include other measures of cognition, psychopathology, safety measures and biological measures.
CONCLUSIONS: SPIRO-TREAT is the first study evaluating the efficacy of the mineralocorticoid receptor antagonist spironolactone to improve cognitive impairments in schizophrenia patients targeting the NRG1-ERBB4 signaling pathway. With SPIRO-TREAT, we intend to investigate a novel treatment option for cognitive impairments in schizophrenia that goes beyond the established concepts of interfering with dopaminergic neurotransmission as key pathway in schizophrenia treatment.
CLINICAL TRIAL REGISTRATION: International Clinical Trials Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2014-001968-35-DE.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Contemporary clinical trials communications - 17(2020) vom: 27. März, Seite 100537 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hasan, Alkomiet [VerfasserIn] |
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| Links: |
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| Themen: |
Cognitive impairment |
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| Anmerkungen: |
Date Revised 13.11.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.conctc.2020.100537 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306660326 |
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| 100 | 1 | |a Hasan, Alkomiet |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Add-on spironolactone as antagonist of the NRG1-ERBB4 signaling pathway for the treatment of schizophrenia |b Study design and methodology of a multicenter randomized, placebo-controlled trial |
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| 500 | |a Date Revised 13.11.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2020 The Author(s). | ||
| 520 | |a BACKGROUND: Preclinical studies recently showed that the mineralocorticoid antagonist spironolactone acts also as an antagonist of the NRG1-ERBB4 signaling pathway and improves schizophrenia-like behaviour in Nrg1 transgenic mouse model. As this signaling pathway is critically linked to the pathophysiology of schizophrenia, especially in the context of working-memory dysfunction, spironolactone may be a novel treatment option for patients with schizophrenia targeting cognitive impairments | ||
| 520 | |a AIMS: To evaluate whether spironolactone added to an ongoing antipsychotic treatment improves cognitive functioning in schizophrenia | ||
| 520 | |a METHODS: The add-on spironolactone for the treatment of schizophrenia trial (SPIRO-TREAT) is a multicenter randomized, placebo-controlled trial with three arms (spironolactone 100 mg, spironolactone 200 mg and placebo). Schizophrenia patients are treated for three weeks and then followed-up for additional nine weeks. As primary outcome, we investigate changes in working memory before and at the end of the intervention phase. We will randomize 90 patients. Eighty-one patients are intended to reach the primary endpoint measure at the end of the three-week intervention period. Secondary endpoints include other measures of cognition, psychopathology, safety measures and biological measures | ||
| 520 | |a CONCLUSIONS: SPIRO-TREAT is the first study evaluating the efficacy of the mineralocorticoid receptor antagonist spironolactone to improve cognitive impairments in schizophrenia patients targeting the NRG1-ERBB4 signaling pathway. With SPIRO-TREAT, we intend to investigate a novel treatment option for cognitive impairments in schizophrenia that goes beyond the established concepts of interfering with dopaminergic neurotransmission as key pathway in schizophrenia treatment | ||
| 520 | |a CLINICAL TRIAL REGISTRATION: International Clinical Trials Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2014-001968-35-DE | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cognitive impairment | |
| 650 | 4 | |a Drug repositioning | |
| 650 | 4 | |a Drug repurposing | |
| 650 | 4 | |a NRG1-ERBB4 | |
| 650 | 4 | |a Schizophrenia | |
| 650 | 4 | |a Spironolactone | |
| 700 | 1 | |a Roeh, Astrid |e verfasserin |4 aut | |
| 700 | 1 | |a Leucht, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Langguth, Berthold |e verfasserin |4 aut | |
| 700 | 1 | |a Hansbauer, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a Oviedo-Salcedo, Tatiana |e verfasserin |4 aut | |
| 700 | 1 | |a Kirchner, Sophie K |e verfasserin |4 aut | |
| 700 | 1 | |a Papazova, Irina |e verfasserin |4 aut | |
| 700 | 1 | |a Löhrs, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Wagner, Elias |e verfasserin |4 aut | |
| 700 | 1 | |a Maurus, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Strube, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Rossner, Moritz J |e verfasserin |4 aut | |
| 700 | 1 | |a Wehr, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Bauer, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Heres, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Leucht, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Kreuzer, Peter M |e verfasserin |4 aut | |
| 700 | 1 | |a Zimmermann, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Schneider-Axmann, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Görlitz, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Karch, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Egert-Schwender, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Schossow, Beate |e verfasserin |4 aut | |
| 700 | 1 | |a Rothe, Philipp |e verfasserin |4 aut | |
| 700 | 1 | |a Falkai, Peter |e verfasserin |4 aut | |
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